Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study.

Isidor Minović,Albert-Jan Voerman,Stephan J L Bakker,Lyanne M Kieneker,Robin P F Dullaart,Margery A Connelly,Daan J Touw,Ron T Gansevoort,Rudolf A De Boer,Eelko Hak,Ido P Kema,Manfred Eggersdorfer,Jens Bos

doi:10.3390/nu12092711

Abstract

Background: a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. Methods: we measured plasma pyridoxal 5’-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1–57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8–8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47–0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51–1.01) and 0.74 (95% confidence interval, 0.53–1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27–0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65–1.51). Conclusions: in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.

Highlights

Cardiovascular (CV) diseases are the leading cause of death globally [1]
Vitamin B6 deficiency was more prevalent among women
Point estimates from the sensitivity analyses on the non-imputed dataset, using complex survey design analyses, and after excluding participants taking vitamin B6-containing supplements, were not materially different from the reported data. In this large population-based cohort, we found no evidence for an independent relation between vitamin B6 deficiency, as assessed by plasma pyridoxal 5’-phopshate (PLP) concentration, and increased risk of CV outcome in the overall cohort

Summary

Introduction

The societal burden of CV diseases will likely continue to rise due to aging, lifestyle factors and, paradoxically, better treatment of subclinical CV disease [2]. This underscores the need for non-conventional modifiable factors to complement and improve existing CV risk reduction strategies in the general population. Vitamin B6 deficiency has gained considerable attention as a potential risk factor for CV disease [3,4,5,6]. Vitamin B6 exists predominantly as pyridoxal 5’-phopshate (PLP), which is used clinically to diagnose vitamin B6 deficiency [8]

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